Overview

Ryvu Therapeutics discovers and develops small molecule therapies that address high value emerging targets in oncology.

Our pipeline is built from internally-discovered candidates which make use of diverse therapeutic mechanisms, including programs directed at targets in the areas of transcriptional regulation, synthetic lethality, immuno-oncology and immunometabolism.

Ryvu’s two most advanced programs are currently in clinical trials. SEL120 is a selective CDK8 kinase inhibitor in clinical development for the treatment of acute myeloid leukemia and high-risk myelodysplastic syndromes.

SEL24/MEN1703 is a dual PIM/FLT3 kinase inhibitor in clinical development for the treatment of acute myeloid leukemia. Additional programs include candidates directed at SMARCA2/BRM, adenosine A2A/A2B receptor targets and STING agonists.

  • Clinical
    Projects
  • Immuno-oncology
    & Immunometabolism
  • Synthetic
    Lethality

Clinical Projects

  • SEL120

    CDK8 is a kinase submodule of the mediator complex, involved in both transcriptional activation and repression. CDK8- mediator complex integrates basal transcriptional machinery with the activity of oncogenic transcriptional and epigenetic factors. Targeting CDK8 and...

  • SEL24/MEN1703

    SEL24/MEN1703 is a clinical stage program discovered and developed by Ryvu and licensed to the Menarini Group. SEL24/MEN1703 is a first-in-class, dual PIM/FLT3 kinase inhibitor with a unique activity profile. By design, this profile may...

Immuno-oncology & Immunometabolism

Ryvu Therapeutics has deep expertise in the discovery of small molecule candidates with optimized properties to address specific limitations of existing therapeutic approaches.

To identify these candidates, Ryvu uses platforms based on the most current understanding of how the immune system interacts with cancer cells and how cancer cells function biologically. These immuno-oncology and immunometabolism approaches have a successful history in biopharmaceutical development. Ryvu has accumulated scientific and technical infrastructure that allow high-throughput generation of candidates using these platforms.

  • A2A/A2B

    Accumulation of adenosine is a potent and widespread mechanism that allows the tumor to evade immune surveillance. Adenosine suppresses activation, expansion and cytokine production in many types of immune cells, such as T cells, NK...

  • STING AGONIST

    STING protein is one of the major players in innate immune activation being a potent trigger of type I interferon (IFN) and pro-inflammatory cytokines. STING agonists facilitate cancer antigen recognition specific to individual patient and...

  • HPK1 INHIBITORS

    The high therapeutic potential of HPK1 inhibitors (hematopoietic progenitor kinase 1, MAP4K1) lies in their potential to simultaneously improve T cell function, tumor antigen presentation and combat the immunosuppressive tumor microenvironment.  HPK1 is a negative...

Synthetic Lethality

One of the challenges in the development of new oncology therapeutics is the limited number of protein targets known to be addressable with small molecules. Synthetic lethality allows the identification of novel protein targets and mechanisms of cancer cell sensitivity that can be used therapeutically.

Compounds active on specific synthetic lethal targets selectively kill tumor cells of a precisely defined model system, characterized by a specific genetic, epigenetic or metabolic characteristic. This is the approach actively investigated at Ryvu that allows the generation of compounds with highly specific and well-characterized activity.

  • SMARCA2/BRM

    Ryvu’s develops drugs for genetically determined cancers which had been considered in the past as largely undruggable using rational approaches.  Synthetic lethality allows now for identification of novel unanticipated protein targets, highly effective in a...

  • MTAP DELETIONS

    Deletion of 9p21 locus is one of the most frequent genetic alterations associated with human cancers. Apart from tumor suppressor p16, locus 9p21 contains the gene coding methylthioadenosine phosphorylase (MTAP), the only enzyme capable of...

Novel Targets

Beyond publicly disclosed programs, Ryvu is working on candidates that address novel targets in the areas of synthetic lethality, immuno-oncology and immunometabolism to generate new therapeutics with first-in-class or best-in-class potential.

For the candidates, Ryvu is utilizing a proprietary drug discovery approach combining internally developed expertise and new sophisticated tools and technologies to identify small molecule compounds with favorable profiles and activity.

Collaborations

In 2013, Ryvu and Merck KGaA initiated a joint research strategy involving intensive work on multiple targets and several chemical series. The collaboration has successfully completed two milestones and has been expanded over time with additional targets.

The aim of the partnership with Merck is the development of new anticancer therapeutics acting on diverse biological targets associated with aberrant metabolic pathways in cancer cells. Dependence on specific metabolic pathways is a feature of various types of cancer, therefore, targeting this vulnerability has many potential applications in a broad range of patient populations.

The collaboration has resulted in scientific achievements, the joint filing of patent applications and data presentations at international scientific conferences.

Publications

Society for Immunotherapy of Cancer 34th Annual Meeting (SITC 2019), November 6–10, National Harbor, MD, USA

  • "Novel dual A2A /A2B adenosine receptor antagonists for cancer immunotherapy in vitro characterization"

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  • "Development and characterization of next generation small molecule STING agonists"

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CICON 2019 – Translating Science into Survival – September 25-28, 2019, Paris, France

  • “Characterization of novel potent dual A2A/A2B adenosine receptor antagonists for cancer immunotherapy”

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24th Congress of EHA, June 13-16, 2019 Amsterdam, Netherlands

  • "CLI24-001: First-in-human study of SEL24/MEN1703, an oral dual PIM/FLT3 kinase inhibitor, in patients with acute myeloid leukemia"

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ASCO Annual Meeting 2019, May 31-June 4, Chicago, IL, USA

  • "CLI24-001: First-in-human study of SEL24/MEN1703, an oral dual PIM/FLT3 kinase inhibitor, in patients with acute myeloid leukemia"

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